Tubular articles

ABSTRACT

Tubular articles such as condoms or catheters are rendered antimicrobially effective by incorporating therein an effective amount of a non-ionic sparingly water soluble antimicrobial agent. Preferably the antimicrobial is triclosan and the tubular article is a condom made from natural rubber latex. A method of manufacturing the tubular articles is described in which the anti-microbial agent is incorporated into the material forming the article before the article is formed.

This invention relates to tubular articles such as condoms or cathetersrendered antimicrobially effective by incorporating therein an effectiveamount of a non-ionic sparingly water soluble antimicrobial agent suchas triclosan into the material such as natural rubber from which thearticle is made.

For many elastomeric tubular articles which are used in the medical orveterinary sciences it is often desirable to treat them so they canprevent the passage of bacteria or virus or even have a microbiocidaleffect at least at their surfaces. Such articles include catheters sucha urethral catheters, condoms, wound drains, endotracheal tubes and thelike. Heretofore such articles have been treated with antimicrobialagents by washing with a solution of the agent or by treating it with acream or lubricating oil or powders which contain an antimicrobialagent.

It would be useful if the aforementioned articles could be manufacturedwith the antimicrobial agent in situ. Unfortunately it has proved to beextremely difficult to produce articles made of rubbers such as naturalrubber latex or the like incorporating an antimicrobial agent. Forexample, the agents have tendency to destabalise the materials fromwhich the article is formed, for example by causing gelling of a latex.However, a method has now been discovered which allows articles to beformed which incorporate an antimicrobially effective amount of an agentwhich reduces the tendency for bacteria to grow on the surface of thearticle and then improves the barrier properties of the article againsttransmission of bacteria and even of viruses such as the HIV andhepatitis B virus.

The present invention provides a method for the manufacture of anantimicrobially effective tubular article which comprises including anantimicrobially effective amount of a non-ionic sparingly water solubleantimicrobial agent in an aqueous dispersion of the article materialprior to forming the article.

The present invention also provides an antimicrobial tubular articlewhich contains a non-ionic sparingly water soluble antimicrobial agent.

The antimicrobial agent is non-ionic at neutral pH values and onlysparingly soluble in water. By sparingly water soluble it is meant thatthe antimicrobial agent has a solubility in water at 20° C. of less than0.1 gm/liter, preferably less than 0.05 gm/liter.

The article material will contain (i.e. within its body as opposed toresiding only on its surface) an antimicrobially effective amount ofantimicrobial agent. Suitably the article material may contain from 0.1to 10% w/w of antimicrobial agent, more suitably 1 to 5% w/w andpreferably about 1.0% ww.

The material which forms the article can be any one of those which areconventionally used for forming such articles especially condoms andinclude natural rubber, polyvinyl chloride and polyurethane. The use ofa natural rubber latex to form the article material is preferred. Theuse of a non-ionic sparingly soluble antimicrobial agent in a naturalrubber latex article offers a method of overcoming many of the potentialproblems which could occur with natural rubber latex articles if theyare susceptible to penetration by virus such as those responsible forAIDS and Hepatitis B.

From the foregoing it will be appreciated that in a preferred aspectthis invention provides a natural rubber latex tubular article whichcontains a non-ionic, sparingly soluble antimicrobial agent.

The preferred antimicrobial agent is 2,4,4'-trichloro-2'-hydroxydiphenylether (triclosan).

Thus in a preferred aspect the present invention provides a naturalrubber latex tubular article which contains2,4,4'-trichloro-2'-hydroxydiphenyl ether.

These antimicrobial agents are particularly suitable for incorporationinto catheters and condoms formed from natural rubber latex. It has beenobserved that natural rubber latices may be coagulated by ionicantimicrobial agent. If articles formed from natural rubber latices areto be treated with such antimicrobial agents in the prior art, it isonly after the rubber has been vulcanised that this can be achieved. Thenature of the surface of cured rubber articles is such as to be notreadily coated or impregnated with for example an antimicrobial agent.Methods of overcoming this problem have included coating the articlewith the antimicrobial agent in a binding agent modifying the rubbersurface to make it responsive to binding the antimicrobial agent or bytreating the surface with a solvent to cause the rubber to swell andthen impregnating with the antimicrobial agent in the same or anothersolvent and finally removing the solvent. These processes are difficultto carry out and do not give a consistent product. Surprisingly it hasbeen found that non-ionic, sparingly water soluble antimicrobial agentsdo not coagulate natural rubber latex. This enables the antimicrobialagent to be uniformly mixed with the rubber latex in the fluid pre-curedstate which makes manufacture of rubber articles made therefrom easieras it requires no post-cure operations on the article and can alsoprovide a more consistent product. The low solubility of theantimicrobial agent means that it is not removed during the leachingstep in the tubular article manufacturing process yet the antimicrobialagent is found to be effectively released from both the inside andoutside of the article under conditions of which simulate wear.

Suitable non-ionic, sparingly soluble antimicrobial agents includephenol derivatives such as chlorophene, dichloroxylenol,hexachloraphane; diphenyl derivatives, halogenated hydroxy diphenylderivatives such as diphenyl ethers for example2,4,4'-trichloro-2'-hydroxy diphenyl ether (triclosan); and agents suchas diacetylamino-azotoluene and triclocarban. The preferredantimicrobial agent is triclosan.

The articles containing antimicrobial agent may be prepared by mixingthe required amount of agent with the article material, for example anaqueous dispersion such as a natural rubber latex. The agent may havebeen previously formed into a dispersion by mixing with a little of thelatex or by mixing with water and dispersing agents. The rest of thelatex may be gradually mixed with this dispersion until a homogenousmixture results. The article is then formed in the usual manner.

Thus, a former may be first dipped into a coagulant solution and allowedto dry. Thereafter the coated former is dipped into the latex, removed,dried and immersed in a leaching bath. After drying the article may thenbe `cured`. Alternatively, condoms or catheters may be prepared byconventional processes not employing coagulatants, for example acidgellation or heat gellation as well as multivalent cation gellation.Condoms are most aptly prepared by the conventional double dippingprocess.

In a process described above the antimicrobial agent may be distributedthrough the whole of the article material if desired so that the agentmay be released from both the inside and the outside of the article.However, it may be desirable for some purposes to have the agentavailable only on the inside or wearer-contacting surface of thearticle. The agent may be present therefore in the material which formsthe last coat on the former, that is becomes the inside of the articlewhen the article is removed from the former. Thus with a condom thevaginal flora is less likely to be disturbed. Reversing the method whenproducing a catheter means that a product can be produced where most ofthe antibacterial agent can be available on the outside of the catheter.

It will be understood that in a preferred aspect this invention providesa thin polymer condom which contains 2,4,4¹ -trichloro-2¹-hydroxydiphenyl ether (triclosan).

Such condoms incorporating a non-ionic sparingly water solubleantimicrobial agent offer the user a higher degree of protection fromcommon infecting organisms that might penetrate through anydiscontinuity in the condom.

The present invention provides a method of reducing the risk ofinfection which comprises using thin polymer condom which contain 2,4,4¹-trichloro-2¹ -hydroxydiphenyl ether (triclosan). The condom contains anantimicrobially effective amount of triclosan. The triclosan provides aprotection for the period of use by improving the barrier property ofthe condom, for example with respect to HIV.

In a further preferred aspect the present invention provides a condomwhich contains a non-ionic, sparingly water soluble antimicrobial agentand which has at least on the inside surface thereof a powder containingtriclosan.

The powder may contain an antimicrobially effective amount of triclosan.The powder may suitably contain from 0.1 to 10% w/w of triclosan, moresuitably may contain from 0.5 to 8% w/w and preferably contains about 1%w/w.

The powder containing an antimicrobially effective amount of triclosanmay be obtained by methods which comprise mixing of the ingredients.Suitable methods include (a) mixing a solution of triclosan in acetonewith the powder, drying, grinding and sieving the resulting powder toremove large particles and (b) mixing the dry powders together.

The powder containing triclosan may be coated onto the inside of thecondom incorporating the non-ionic, sparingly water solubleantimicrobial agent such as triclosan itself in the way lubricatingpowders are conventionally applied.

The article according to this invention may also contain a furtherantibacterial agent is desired, for example chlorhexidine digluconate.

The following examples illustrate the invention.

EXAMPLE 1

A condom former of glass is thoroughly washed using dilute acid oralkali solutions. The former is rinsed in soft water and dried. Theformer is dipped into the natural rubber latex. The former is removedand the latex coating dried and evenly distributed over the former byrotation and agitation of the former. The former is then dipped a secondtime into the latex since a second layer of latex reduces the chance ofany pin-holes remaining in the final product. The former is removed andthe second coat dried. The article is then leached in a tank of warmwater at 70° C. for two minutes. After leaching the former is dipped inan aqueous solution containing 10% w/w of chlorhexidine digluconate for20 seconds and then removed and shaken to remove any adhering waterdroplets.

The rubber latex contained 1% by weight of triclosan. This was preparedas follows:

The hydroxy halogenated biphenyl ether 2,4,4¹ -trichloro-2¹ -hydroxydiphenyl ether (triclosan) was incorporated into a natural rubber latexby mixing triclosan (21 g) with a small quantity of latex to form apaste. The latex was gradually diluted with more latex until therequired concentration was achieved. The final latex formulation was:

Latex (42%) 4940 g

Triclosan 21 g

EXAMPLE 2

The procedure of Example 1 was repeated omitting the chlorhexidine step.

EXAMPLE 3

The procedure of Example 2 was repeated but the triclosan wasincorporated into the first latex only.

EXAMPLE 4

A catheter is prepared by a multiple dipping process whereby a former ofappropriate size is repeatedly dipped in a bath of pre-vulcanised rubberlatex to build up layers of rubber to give the required wall thickness.The final latex dip incorporated 1% triclosan (based on solids contentof latex).

I claim:
 1. A method for the manufacture of an antimicrobially effectivetubular article which comprises including an antimicrobially effectiveamount of a non-ionic sparingly water soluble antimicrobial agent in anaqueous dispersion of the article material prior to forming the article.2. A tubular article produced by the inclusion of an antimicrobiallyeffective amount of a non-ionic sparingly water soluble antimicrobialagent in an aqueous dispersion of the article material prior to formingthe article.
 3. A method as claimed in claim 1 wherein the antimicrobialagent is 2,4,4¹ -trichloro-2¹ -hydroxydiphenyl ether.
 4. A method asclaimed in claim 3 wherein the article is a condom.
 5. A method asclaimed in claim 3 wherein the article is a catheter.
 6. A method asclaimed in claim 1 wherein the material is a natural rubber latex.
 7. Anarticle as claimed in claim 2 wherein the antimicrobial agent is 2,4,4¹-trichloro-2¹ -hydroxydiphenyl ether.
 8. An article as claimed in claim7 which is a condom.
 9. An article as claimed in claim 8 which is acatheter.
 10. An article as claimed in claim 2 wherein the material isnatural rubber.
 11. A method as claimed in claim 1, wherein anantimicrobially effective amount of 2,4,4'-trichloro-2'-hydroxydiphenylether is included in a natural rubber latex, which is thereafter formedinto a condom.
 12. A method as claimed in claim 1, wherein anantimicrobially effective amount of 2,4,4'-trichloro-2'-hydroxydiphenylether is included in a natural rubber latex, which is thereafter formedinto a catheter.
 13. An article as claimed in claim 2, wherein saidantimicrobial agent is 2,4,4'-trichloro-2'-hydroxydiphenyl ether, saidaqueous dispersion is a natural rubber latex and said article is acondom.
 14. An article as claimed in claim 2, wherein said antimicrobialagent is 2,4,4'-trichloro-2'-hydroxydiphenyl ether, said aqueousdispersion is a natural rubber latex and said article is a catheter.